Preparation of beta-alanine



Patented Mar. 16, 1954 PREPARATION OF fl-ALANINE Albert S. Matlaek, Wilmington, Del., assignor to Hercules Powder Company, Wilmington, Del., a corporation of Delaware No Drawing. Application July 5, 1952, Serial No. 297,385

3 Claims. (01. 260-534) 1 2 This invention relates to a new process of etc; the alkali metal salts of triphenylmethane synthesizing p-alanine and, more particularly, to such as triphenylmethyl sodium, etc; and the a process for preparing ,B-alanine from acrylalkali metals themselves such as sodium, potasamide. sium, etc. Thus, the strongly basic catalyst may fi-Alanine is an important amino acid and be defined as one having a basic strength that is many attempts have been made to discover some at least as strong as that of potassium hydroxide. means by which it could be synthesized by a low- The basic compound acts as a true catalyst for cost commercial process, but to date all of the this polymerization reaction and hence any processes for preparing c-ala-nine are costly amount of it may be used from a catalytic amount either because of the expensive reagents utilized in up to a large excess, if desired. In general, an in its synthesis or because of the low yields amount of from about 0.03% to about 1% based which are obtained. Consequently, the price of on the weight of the monomer is used. c-alanine has remained at a high level and is, in The polymerization may be carried out either fact, prohibitive for the use of this amino acid in the presence or absence of an inert liquid in many applications. is diluent. In either case, it should be carried out Now, in accordance with this invention, a in a nonaqueous medium, i. e., under substantialmethod has been discovered whereby c-alanine ly anhydrous conditions to avoid decomposition may be produced in high overall yields from a of the basic catalyst and addition of water to relatively inexpensive starting material, acrylthe double bond of the acrylamide. Bulk polyamide, by a simply and easily operated process. merization is generally preferred inasmuch as The process of this invention is carried out by it is then not necessary to remove the inert liqcontacting acrylamide with a strongly basic uid diluent either before or after the hydrolysis catalyst to produceapolymeric intermediate mastep which follows. However, it is possible to terial which is hydrolyzed by heating it with an carry out the polymerization stage by a solution aqueous solution of an acid or base. The reprocess using a liquid which is inert under the actions involved in this synthesis are believed to reaction conditions as diluent. For example, the be as follows: process may be carried out in the presence of One of the advantages of this process is that the hydrolysis step may be carried out directly after the polymer formation without the necessity of isolating or fractionating the intermediate polymer.

The acrylamide is polymerized by contacting it with a strongly basic catalyst under substantially anhydrous conditions. Any strongly basic catalyst may be used to catalyze the polymerization. Exemplary of the catalysts that may be erally is such an amount as to provide solutions used are the strongly basic hydroxides, as, for containing from about 2% to about 50% of example, the alkali metal hydroxides such as acrylamide, and preferably from about 10% to sodium and potassium hydroxide, and quater- 20% of acrylamide. y mm nium hy r xide such as benzyltri- The temperature at which the polymerization methylammonium hydroxide; the alkali metal step is carried out may be varied over a wide alkoxides such as sodium methoxide, sodium range, depending on the'activity of the catalyst, ethOXide, i m rfiutoxide, etc, and th c rwhether a solvent is used, etc. For example, if responding potassium alkoxides; the alkali" metal amides such as sodamide, potassium amide, etc.; a temperature of from about 25 to about 200 alkali metal hydrides such as sodium hydride, C. may be used, and preferably a temperature inert organic diluents such as the hydrocarbon solvents, as, for example, hexane, heptane, octane, benzene, toluene, etc.; the tertiary a1- cohols such as tert-butanol, tert-amyl alcohol, 30 etc; ethers such as dioxane, dibutyl ether, di-

phenyl ether, etc.; basic solvents such as pyridine, quinoline, etc. It may also be carried out in such a diluent as liquid ammonia. Any desired amount of solvent may be used, but gen carried out in bulk or ina'n inert organic diluent,"

of from about 80 to about 110 C. may be used. If the polymerization is carried out in liquid ammonia, temperatures as low as -40 C. may be used with a catalyst such as sodamide.

Since acrylamide readily undergoes a radicalinduced polymerization, it is usually preferable to add an inhibitor for this type of polymerization. Any of the compounds which are wellknown to inhibit radical-induced polymerization may be used, as, for example, hydroquinone, quinone, phenyl c-naphthylamine, etc., but preferably the inhibitor is a nonhydroxylic inhibitor since a higher molecular weight intermediate is obtained when this type of inhibitor is used. The amount of such an inhibitor which is added may, of course, vary over a wide range, but generally is within the range of from about 0.005% to about 0.1 based on the weight of acrylamide.

The amount of time required for this first stage in the process of this invention will depend upon the temperature, catalyst, and whether or not an inert diluent is used. For example, if the polymerization is carried out by a bulk process, a high molecular weight intermediate is obtained within a few minutes, but a longer time may be required if the polymerization is carried out by a solution process. The extent to which the polymerization reaction is carried out is not critical insofar as the overall process is concerned. However, for higher yields of fl-alanine and reduction in the contamination which is introduced by the presence of the vinyl end group in the polymer, it is preferable that the intermediate have attained a degree of polymerization of at least 10. Usually the base-catalyzed polymerization is allowed to proceed to as high a degree of polymerization as will be produced in a reasonable length of time.

As pointed out above, the hydrolysis of the intermediate polymer may usually be carried out directly on the reaction mixture. Such is the case when the polymerization is carried out in bulk or in an inert organic diluent unless the organic diluent is water miscible, in which case it would be preferable, for the sake of economical operation, to remove the solvent by filtration, distillation, or other means before the hydrolysis step. However, when liquid ammonia, or any other solvent which reacts with the hydrolytic agent which is used in the next step, is used as the diluent, it is, of course, necessary to remove the solvent before proceeding with the hydrolysis step.

The hydrolysis of this intermediate polymeric material is readily carried out by adding water and an acid or base and then heating the reaction mixture until the hydrolysis is complete. Any strong mineral acid may be used to catalyze this hydrolysis reaction; as, for example, a mineral acid such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, hydriodic acid, or an organic acid such as trichloroacetic acid may be used. The concentration of the aqueous acid solution which is added is not critical, but generally a concentration of from about 20% to about 50% is used. The hydrolysis may also be carried out with a base, as, for example, an alkali metal hydroxide such as sodium or potassium hydroxide, an alkaline earth metal hydroxide such as barium or calcium hydroxide, etc. The temperature at which this hydrolysis step is carried out may be varied over a wide range, the lower limit being that at which the hydrolysis proceeds at a reasonable rate andthe upper limit by the stability of ,S-alanine or its salts in the hydrolysis medium. For example, if a base, such'as barium hydroxide,

is used to carry out the hydrolysis, higher temperatures and longer reaction times are required than those which are necessary when an acid is used as the hydrolytic agent. Under such circumstances it may be desirable to operate the reaction under pressure and at temperatures up to about 200 C. to bring about the hydrolysis in a reasonable length of time. Thus, the hydrolysis step may be carried out at temperatures of from about 50 C. to about 200 C., and preferably is carried out at temperatures of from about C. to about C. The time required for the hydrolysis step will vary with the strength of the acid or base being used as the hydrolytic agent, the temperature, etc. Usually it is suificient to heat the polymer with the hydrolytic agent at a reflux temperature for a short length of time.

The method by which the fl-a-lanine is separated and purified will depend upon the process used for its preparation. If an acid is used to catalyze the hydrolysis reaction, it may be removed from the hydrolyzate by any of the usual means, as, for example, it may be neutralized with a compound which will form an insoluble salt with the acid anion, as, for example, barium hydroxide, barium carbonate, calcium hydroxide, calcium carbonate, etc. The acid may also be removed by means of an anion exchange resin or by any other desired means. Thus, if sulfuric acid is used, then any neutraliz ng agent which forms a water-insoluble substance with sulfuric acid may be used to remove the excess acid. If a carbonate is used for this purpose, the ,B-alanine will be isolated as its sulfate which must then be treated with an alkaline earth hydroxide to liberate the amino acid. If hydrochloric acid is used as the hydrolytic agent, the ;8-alanine may be recovered from its hydrochloride with triethylamine or any of the other usual means. If a basic hydrolysis is carried out, the fi-alanine will be recovered as its metal salt and an acid will be required to liberate the free alanine. In the case of the use of barium or calcium hydroxide, carbon dioxide may be used to obtain the free fi-alan ne. The fi-alanine may be further purified by recrystallization from any suitable solvent, as, for example, aqueous methanol, etc.

The following example will illustrate the process of this invention.

Example To a mixture of 10 parts of acrylamide and 0.05 part of phenyl fi-naphthylamine was added a solution of 0.4 part of sodium in 15 parts of tert-butanol. The tert-butanol was removed. in vacuo at 40 C. and the reaction mixture was then heated to form a homogeneous melt. A vigorous exothermic reaction set in and the reaction was complete within 2 to 3 minutes. An excess (40 parts) of 50% aqueous sulfuric acid was added and the reaction mixture was heated under reflux for 4 hours. It was then neutralized toa pH of '7 with hot aqueous barium hydroxide. The barium sulfate was removed by filtration and the precipitate was washed twice with water. The combined filtrates were evaporated to dryness in vacuo whereby a sirup was obtained which crystallized on cooling. This crystalline material amounted to a yield of 90% of p-alanine based on acrylamide used. On recrystallization from hot methanol, it was found to have a meltin point of 196" 0.,and a mixed melting point of it with a known sample of fl alani'ne was not depressed.

What I claim and desire to protect by Letters Patent is:

1. The process of preparing fl-alanine which comprises contacting acrylamide with a strongly basic catalyst, adding an aqueous solution of a hydrolytic agent to the polymeric material so obtained, and heating until said polymeric material is hydrolyzed.

2. The process of preparing fl-alanine which comprises contacting acrylamide with a strongly basic catalyst at a temperature of from about C. to about 200 0., adding to the polymer so obtained an aqueoussolution of an acid, and heating the reaction mixture to a temperature of from about C. to about 200 C. until the polymer is hydrolyzed.

3. The process of preparing p-alanine which comprises contacting acrylamide with a strongly basic catalyst at a temperature of from about C. to about 0., adding to the polymer so obtained an aqueous solution of an acid, and heating the reaction mixture to a temperature of from about 80 C. to about C. until the polymer is hydrolyzed.

ALBERT S. MATLACK.

References Cited in the file of this patent UNITED STATES PATENTS 

1. THE PROCESS OF PREPARING B-ALANINE WHICH COMPRISES CONTACTING ACRYLAMIDE WITH A STRONGLY BASIC CATALYST, ADDING AN AQUEOUS SOLUTION OF A HYDROLYTIC AGENT TO THE POLYMERIC MATERIAL SO OBTAINED, AND HEATING UNTIL SAID POLYMERIC MATERIAL IS HYDROLYZED. 